A Paper-Based Synthetic Biology Platform for the On-Demand Testing of Water Quality

用于水质按需检测的纸质合成生物学平台

基本信息

批准号：
10483253
负责人：
Khalid Kamal Alam
金额：
$ 77.68万
依托单位：
STEMLOOP, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-20 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10483253
关键词：
Address Adoption Aging Americas Analytical Chemistry Area Awareness Biochemical Biochemical Reaction Biosensing Techniques Biosensor Cell-Free System Cells Characteristics Chronic Collection Communities Companions Consumption Contractor Dangerousness Detection Development Developmental Disabilities Devices Diagnostic Reagent Kits Diagnostic Sensitivity Engineering Ensure Environment Event Exposure to Eye Filtration Flushing Funding Genetic Goals Gold Health Heavy Metals Homologous Gene Household Inequality Infrastructure Instruction Interview Investments Laboratories Lateral Lead Lead levels Life Ligands Logistics Methods Microfluidic Microchips Molecular Monitor Outcome Paper Performance Phase Plumbing Poison Positioning Attribute Procedures Process Production Proteins Public Health Quality Control Reaction Reporter Genes Running Safety Sampling Schools Sensitivity and Specificity Series Shipping Signal Transduction Site Source System Technical Expertise Techniques Technology Testing Time Toxin Transportation United States Validation Visual Visualization Water Water Pollutants Water Supply Work Zinc aged anthropogenesis base chronic Pb exposure contaminated drinking water cost cross reactivity design drinking water field study hazard home test human centered design improved innovation interest lead contamination lead exposure manufacturing scale-up microorganism mobile application operation physically handicapped preservation prototype quality assurance remediation response risk mitigation scale up screening sensor technology success synthetic biology technology validation tool transcription factor usability validation studies water quality water sampling water testing

项目摘要

PROJECT SUMMARY/ABSTRACT Safe drinking water is essential for public health yet is increasingly threatened by anthropogenic activities and aging infrastructure that contaminate it with heavy metals and other toxins. Most notable in the United States is the contamination of drinking water with lead, a heavy metal that is pervasive in America’s water infrastructure and indoor plumbing. Chronic exposure to lead results in numerous adverse health and societal outcomes and is an environmental injustice that widens inequalities. Upon discovery, lead contamination can be mitigated by changing drinking water source, flushing, and existing filtration technologies. However, as recent events such as the crises in Flint, MI or Newark, NJ exemplify, improper management can lead to major public health threats by creating community-wide exposure to dangerously high levels of lead. Lead contamination of drinking water is widespread across the United States due to aged infrastructure and domestic plumbing that heavily relied on lead. Frequent monitoring for the presence of lead contamination in drinking water is part of the solution. It can identify where problems exist, alert consumers without delay, and inform risk mitigation and remediation strategies. However, reliable testing remains limited to analytical chemistry techniques that are costly, time consuming, and require substantial laboratory infrastructure and technical expertise. This complicates the large- scale of testing needed to address the lead in drinking water crisis and is a barrier to the routine testing of water supplies by consumers. Here, we propose to address these issues by pursuing the next stage of development of our technology platform that will allow for the reliable, inexpensive, on-site, and on-demand monitoring of lead in drinking water. Our technology is built from recent innovations in synthetic biology that allow us to repurpose biological sensor proteins that detect specific toxic ligands, such as heavy metals, into ‘cell-free’ reactions that produce detectable signals when lead is present. These biochemical reactions are safe and can be embedded on paper devices for long term storage and distribution. Adding water to these paper-based devices activates the biochemical reaction and produces a visual signal in the presence of a toxic compound. This Phase II proposal details a series of complementary aims for achieving improved specificity and sensitivity of this lead testing device, using a human-centered design process to improve test operation and results interpretation, and adapting our manufacturing and quality assurance/quality control processes for a scale-up of manufacturing capability for validation studies. A successful outcome of this proposal will lead to a rapid lead test with sensitivity comparable to laboratory testing, an accessible and easy-to-use device format with a companion mobile app, and pilot-scale production to validate our lead sensing technology in the laboratory and in the field. This work will enable manufacturing and commercial distribution of a highly sensitive and rapid lead biosensor, which will help address the growing water quality crisis in the United States and beyond.

项目概要/摘要安全饮用水对于公共卫生至关重要，但日益受到人类活动和老化的基础设施受到重金属和其他毒素的污染，其中最引人注目的是美国。饮用水被铅污染，铅是美国水利基础设施中普遍存在的一种重金属和室内管道。长期接触铅会导致许多不良的健康和社会后果。铅污染是一种扩大不平等的环境不公正现象，一旦发现，可以通过以下方式减轻。然而，正如最近发生的事件一样，改变饮用水源、冲洗和现有的过滤技术。正如密歇根州弗林特或新泽西州纽瓦克的危机所表明的那样，管理不当可能导致重大公共卫生威胁导致整个社区暴露于危险的高浓度饮用水铅污染中。由于严重依赖老化的基础设施和国内管道，这种情况在美国各地很普遍经常监测饮用水中是否存在铅污染是解决方案的一部分。确定存在问题的地方，立即提醒消费者，并告知风险缓解和补救措施然而，可靠的测试仍然局限于昂贵、耗时的分析化学技术。消耗，并且需要大量的实验室基础设施和技术专业知识，这使大规模的复杂化。解决饮用水危机所需的检测规模是常规水检测的障碍在这里，我们建议通过下一阶段的发展来解决这些问题。我们的技术平台将允许对铅进行可靠、廉价、现场和按需的监测我们的技术基于合成生物学的最新创新，使我们能够重新利用它。生物传感器蛋白可检测特定的有毒配体，例如重金属，并将其转化为“无细胞”反应当存在铅时，会产生可检测到的信号。安全且可嵌入用于长期储存和分配的纸质设备上添加水会激活这些纸质设备。在有毒化合物存在的情况下发生生化反应并产生视觉信号。提案详细说明了一系列补充目标，以提高该先导药物的特异性和敏感性测试设备，采用以人为本的设计流程来改进测试操作和结果解释，以及调整我们的制造和质量保证/质量控制流程以扩大制造规模该提案的成功结果将导致快速且灵敏的先导测试。与实验室测试相媲美，一种易于使用的设备格式，带有配套的移动应用程序，和中试规模生产，以在实验室和现场验证我们的领先传感技术。将使敏感的高度快速的先导生物传感器的制造和商业分销成为可能，这将帮助解决美国及其他地区日益严重的水质危机。